A prospective case control study of functional outcomes and related quality of life after colectomy for neoplasia.

AIM: Our aim was to assess bowel function and its effect on overall quality of life (QOL) when compared to healthy controls after colectomy. METHODS: Patients undergoing resection of colorectal neoplasia were recruited pre-operatively and followed up at 6 and 12 months, to assess 'early' bowel function. Patients who underwent surgery 2 to 4 years previously were recruited for assessment of 'intermediate' bowel function. Healthy relatives were recruited as controls. The Memorial Sloan-Kettering Cancer Centre and EQ-5D questionnaires were used to assess bowel function and QOL, respectively. Statistical assessment included regression analyses, parametric and non-parametric tests. The association between QOL and Memorial Sloan-Kettering Cancer Centre (MSKCC) scores was evaluated using Spearman's rank correlation. RESULTS: Ninety-one patients were recruited for assessment of 'early' and 85 for 'intermediate' bowel function. There were 85 controls. Patients had a significantly higher number of bowel movements at each follow-up (p < 0.001). At 12 months after surgery, patients reported difficulty with gas-stool discrimination. The 'intermediate' group were found to have lower scores for flatus control (<0.001) and total frequency score (p 0.03), indicating worse function. Patients with higher total MSKCC scores, no symptoms of urgency and those able to control flatus reported better QOL (p 0.006, 0.007 and 0.005, respectively) at 6 and 12 months. Gas-stool differentiation and complete evacuation correlated with better QOL in the 'intermediate' bowel function group (p 0.02 and 0.02, respectively). CONCLUSION: Colonic resection adversely affects elements of bowel function up to 4 years after surgery. Good colonic function, represented by higher MSKCC scores, correlates with better QOL

The filtering equations revisited

The problem of nonlinear filtering has engendered a surprising number of mathematical techniques for its treatment. A notable example is the change-of--probability-measure method originally introduced by Kallianpur and Striebel to derive the filtering equations and the Bayes-like formula that bears their names. More recent work, however, has generally preferred other methods. In this paper, we reconsider the change-of-measure approach to the derivation of the filtering equations and show that many of the technical conditions present in previous work can be relaxed. The filtering equations are established for general Markov signal processes that can be described by a martingale-problem formulation. Two specific applications are treated

What is the correct cost functional for variational data assimilation?

Variational approaches to data assimilation, and weakly constrained four dimensional variation (WC-4DVar) in particular, are important in the geosciences but also in other communities (often under different names). The cost functions and the resulting optimal trajectories may have a probabilistic interpretation, for instance by linking data assimilation with maximum aposteriori (MAP) estimation. This is possible in particular if the unknown trajectory is modelled as the solution of a stochastic differential equation (SDE), as is increasingly the case in weather forecasting and climate modelling. In this situation, the MAP estimator (or “most probable path” of the SDE) is obtained by minimising the Onsager–Machlup functional. Although this fact is well known, there seems to be some confusion in the literature, with the energy (or “least squares”) functional sometimes been claimed to yield the most probable path. The first aim of this paper is to address this confusion and show that the energy functional does not, in general, provide the most probable path. The second aim is to discuss the implications in practice. Although the mentioned results pertain to stochastic models in continuous time, they do have consequences in practice where SDE’s are approximated by discrete time schemes. It turns out that using an approximation to the SDE and calculating its most probable path does not necessarily yield a good approximation to the most probable path of the SDE proper. This suggest that even in discrete time, a version of the Onsager–Machlup functional should be used, rather than the energy functional, at least if the solution is to be interpreted as a MAP estimator

Lack of cardioprotection from subcutaneously and preischemic administered Liraglutide in a closed chest porcine ischemia reperfusion model

<p>Abstract</p> <p>Background</p> <p>Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with Liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model.</p> <p>Methods</p> <p>Danish Landrace Pigs (70–80 kg) were randomly assigned to Liraglutide (10 μg/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate.</p> <p>Results</p> <p>The infarct size in relation to ischemic risk region in the control versus the Liraglutide group did not differ significantly: 0.46 ± 0.14 and 0.54 ± 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the Liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly.</p> <p>Conclusion</p> <p>Liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.</p

Mortality after Hospitalization for Pneumonia among Individuals with HIV, 1995–2008: A Danish Cohort Study

BACKGROUND: HIV-infected persons are at increased risk of pneumonia, even with highly active antiretroviral treatment (HAART). We examined the impact of pneumonia on mortality and identified prognostic factors for death among HIV-infected. METHODOLOGY/PRINCIPAL FINDINGS: In a nationwide, population-based cohort of individuals with HIV, we included persons hospitalized with pneumonia from the Danish National Hospital Registry and obtained mortality data from the Danish Civil Registration System. Comparing individuals with and without pneumonia, we used Poisson regression to estimate relative mortality and logistic regression to examine prognostic factors for death following pneumonia. From January 1, 1995, to July 1, 2008, we observed 699 episodes of first hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%-28.9%) in 1995-1996 to 8.4% (95% CI: 6.1%-11.6%) in 2000-2008. Mortality remained elevated for more than a year after hospitalization for pneumonia: adjusted mortality rate ratio 5.38 (95% CI: 4.27-6.78), 1.80 (95% CI: 1.36-2.37), and 1.62 (95% CI: 1.32-2.00) for days 0-90, 91-365, and 366+, respectively. The following variables predicted mortality within 90 days following hospitalization for pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37-10.4), Charlson Comorbidity Index score > or = 2 (3.86, 95% CI: 2.19-6.78); no current HAART (3.58, 95% CI: 1.83-6.99); history of AIDS (2.46, 95% CI: 1.40-4.32); age per 10 year increase (1.43, 95% CI: 1.11-1.85); and CD4+ cell count < or = 200 (2.52, 95% CI: 1.37-4.65). CONCLUSIONS/SIGNIFICANCE: The first hospitalization for pneumonia among HIV-infected individuals was associated with elevated risk of death up to more than a year later. Use of HAART decreased the risk, independent of current CD4+ cell count. Prognosis following pneumonia improved over calendar time

Single Molecule Fluorescence Image Patterns Linked to Dipole Orientation and Axial Position: Application to Myosin Cross-Bridges in Muscle Fibers

Photoactivatable fluorescent probes developed specifically for single molecule detection extend advantages of single molecule imaging to high probe density regions of cells and tissues. They perform in the native biomolecule environment and have been used to detect both probe position and orientation.Fluorescence emission from a single photoactivated probe captured in an oil immersion, high numerical aperture objective, produces a spatial pattern on the detector that is a linear combination of 6 independent and distinct spatial basis patterns with weighting coefficients specifying emission dipole orientation. Basis patterns are tabulated for single photoactivated probes labeling myosin cross-bridges in a permeabilized muscle fiber undergoing total internal reflection illumination. Emitter proximity to the glass/aqueous interface at the coverslip implies the dipole near-field and dipole power normalization are significant affecters of the basis patterns. Other characteristics of the basis patterns are contributed by field polarization rotation with transmission through the microscope optics and refraction by the filter set. Pattern recognition utilized the generalized linear model, maximum likelihood fitting, for Poisson distributed uncertainties. This fitting method is more appropriate for treating low signal level photon counting data than χ(2) minimization.Results indicate that emission dipole orientation is measurable from the intensity image except for the ambiguity under dipole inversion. The advantage over an alternative method comparing two measured polarized emission intensities using an analyzing polarizer is that information in the intensity spatial distribution provides more constraints on fitted parameters and a single image provides all the information needed. Axial distance dependence in the emission pattern is also exploited to measure relative probe position near focus. Single molecule images from axial scanning fitted simultaneously boost orientation and axial resolution in simulation

Interactions Between Estrogen- and Ah-Receptor Signalling Pathways in Primary Culture of Salmon Hepatocytes Exposed to Nonylphenol and 3,3',4,4'-Tetrachlorobiphenyl (Congener 77)

BACKGROUND: The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) and aryl hydrocarbon receptor (AhR), probably involving all subtypes and other co-factors. The anti-estrogenic activities of AhR agonists have been reported. In teleost fish, exposure to AhR agonists has been associated with reduced Vtg synthesis or impaired gonadal development in both in vivo- and in vitro studies. Inhibitory AhR and ER cross-talk have also been demonstrated in breast cancer cells, rodent uterus and mammary tumors. Previous studies have shown that AhR-agonists potentiate xenoestrogen-induced responses in fish in vivo system. Recently, several studies have shown that AhR-agonists directly activate ERα and induce estrogenic responses in mammalian in vitro systems. In this study, two separate experiments were performed to study the molecular interactions between ER and AhR signalling pathways using different concentration of PCB-77 (an AhR-agonist) and time factor, respectively. Firstly, primary Atlantic salmon hepatocytes were exposed to nonylphenol (NP: 5 μM – an ER agonist) singly or in combination with 0.001, 0.01 and 1 μM PCB-77 and sampled at 48 h post-exposure. Secondly, hepatocytes were exposed to NP (5 μM) or PCB-77 (1 μM) singly or in combination for 12, 24, 48 and 72 h. Samples were analyzed using a validated real-time PCR for genes in the ER pathway or known to be NP-responsive and AhR pathway or known to be PCB-77 responsive. RESULTS: Our data showed a reciprocal inhibitory interaction between NP and PCB-77. PCB-77 produced anti-NP-mediated effect by decreasing the mRNA expression of ER-responsive genes. NP produced anti-AhR mediated effect or as inhibitor of AhRα, AhRR, ARNT, CYP1A1 and UDPGT expression. A novel aspect of the present study is that low (0.001 μM) and medium (0.01 μM) PCB-77 concentrations increased ERα mRNA expression above control and NP exposed levels, and at 12 h post-exposure, PCB-77 exposure alone produced significant elevation of ERα, ERβ and Zr-protein expressions above control levels. CONCLUSION: The findings in the present study demonstrate a complex mode of ER-AhR interactions that were dependent on time of exposure and concentration of individual chemicals (NP and PCB-77). This complex mode of interaction is further supported by the effect of PCB-77 on ERα and ERβ (shown as increase in transcription) with no concurrent activation of Vtg (but Zr-protein) response. These complex interactions between two different classes of ligand-activated receptors provide novel mechanistic insights on signalling pathways. Therefore, the degree of simultaneous interactions between the ER and AhR gene transcripts demonstrated in this study supports the concept of cross-talk between these signalling pathways